The Vaccine Technologies Core (VTC) will serve the essential function of providing state-of-theart technologies and materials required for the research projects described in this program proposal. While numerous NIH-sponsored projects commonly employ available materials and technologies from the private sector, by creating this core, we hope to accelerate the process by which novel immunogens and vaccine deliveries can be designed and provided to collaborating investigators. Toward this end, the VTC will be responsible for: 1) production and characterization of novel envelope protein structures from HIV-lsF162 and subtype C described in Projects 1 and 2 for evaluation in primates vaccine/challenge experiments; 2) construction, development, and production of improved plasmid DNA vaccines encoding HIV env and SIV gag/pol genes that enhance the potency of gene delivery in primates; and 3) the development and production of novel adjuvants and formulations that efficiently deliver and improve the potency of env protein vaccines. In brief, the VTC will be utilized to produce most of the Env and Gag/Pol antigens for the proposed program, i.e., as plasmid DNA-based vaccines, or for administration as recombinant proteins. Moreover, potent DNA delivery technologies will be provided, such as electoporation and polylactide co-glycolide (PLG) microparticles, that have been shown to enhance DNA vaccine potency substantially over naked DNA immunization in primates. The VTC also will provide novel vehicles and adjuvant formulations for delivery of recombinant envelope proteins. The availability of these materials and technologies for evaluation in the proposed vaccine/challenge experiments should accelerate the process of identifying lead HIV vaccine candidates for future clinical evaluation.